Synthesis and Absolute Configuration of (−)-Neuchromenin, a Neurotrophic Metabolite ofEupenicillium javanicum var.meloforme, and Its Enantiomer

Abstract

Both the enantiomers of neuchromenin 1 (2,3-dihydro-8,9-dihydroxy-2-methyl-4H,5H-pyrano[3,2-c][1]benzopyran-4-one) were synthesized starting from the enantiomers of ethyl 3

Anti-Inflammatory and Protein Tyrosine Phosphatase 1B Inhibitory Metabolites from the Antarctic Marine-Derived Fungal Strain Penicillium glabrum SF-7123

“…The 13 C NMR spectra of 1 also displayed signals for a methoxy group at δ C 57.0 (C-12), a methylene carbon at δ C 43.5 (C-3), and a methyl group at δ C 20.6 (C-11). A literature review revealed that the 1 H and 13 C NMR data of 1 were similar to those reported for neuchromenin [13,14], indicating close structural similarity between the two compounds, except for the presence of a methoxy group in 1. A detailed analysis of the COSY and HMBC spectra of 1 (Table 1, Figures S4 and S5) confirmed the planar structure of 1 as a derivative of neuchromenin with the replacement of the hydroxy group by a methoxy group attached to C-9.…”

“…To confirm that the observed anti-inflammatory effects did not arise from their cytotoxicity, the MTT assay was conducted in the presence of the compounds tested, and the results showed that compounds 1-5 were not cytotoxic to these cells at doses up to 80.0 M (data not shown) The NMR data of compound 2 (Figure S6) were almost identical to those of 1, indicating a pyranchromene skeleton typical of citromycetin analogues. A close inspection of the 1 H and 13 C NMR data of compound 2 and their comparison with those found in the literature eventually led to the assignment of the structure of neuchromenin, which has been isolated from the culture broth of Eupenicillium javanicum var. meloforme PF1181.…”

Citromycetins and Bilains A–C: New Aromatic Polyketides and Diketopiperazines from Australian Marine-Derived and Terrestrial Penicillium spp.

“…Given that cis-bis(methylthio)silvatin (15) is a compound of known absolute stereochemistry and that the sample of 15 reisolated from P. bilaii (a) possesses the same optical rotation sign as previously reported, 11 (b) is a co-metabolite with bilains A-C, and (c) exhibits an excellent NMR comparison about the diketopiperazine moiety with bilains A-C (16)(17)(18), then on biosynthetic grounds we propose that 15-18 share a common C-3 and C-6 absolute stereochemistry. Unfortunately the low isolated yields of 17 and 18, combined with very low rotational values, precluded the accurate measurement of optical rotations.…”

“…8 To the best of our knowledge, known analogues of cis-bis(methylthio)silvatin (15) are limited to a trans stereoisomer described as co-occurring with 15 in a saltwater fermentation of the terrestrial fungus Coriolus consors. 19 Careful analysis of P. bilaiicometabolites revealed a number of potential new cis-bis(methylthio) silvatin analogues, which we have identified as bilains A-C (16)(17)(18).…”

“…This fractionation also yielded the known siderophore pistillarin (11) [3][4][5] and the known diketopiperazines cyclo-(L-Phe-L-Pro) (12), 6 cyclo-(L-Pro-L-Tyr) (13), 7 and cyclo-(L-Pro-L-Val) (14). 6 Repeated HPLC fractionation of the less polar material yielded the known diketopiperazine cis-bis(methylthio)silvatin (15) 8 along with three new diketopiperazines, bilains A-C (16)(17)(18).…”